The overall objective of this project is to elucidate pathogenetic mechanisms of interstitial lung disease. The proposed experiments will test and the hypothesis that changes from normal in glycosaminoglycan synthesis and distribution are an integral part of injury and repair of the lung interstitium and may be related to changes in other connective tissue components, i.e. collagen and elastin. Initial studies will measure glycosaminoglycan turnover in Bleomycin-treated and control Syrian hamsters using a labelled precursor (35S) to these molecules. Abnormalities in glycosaminoglycan turnover in diseased lungs will be correlated with histiologically determined level of severity of interstitial injury and additionally compared with earlier results with N-nitroso-N-methylurethane induced interstitial disease to assess the role of the specific etiological agent in effecting changes in glycosaminoglycan synthesis. The pattern of labelling of glycosaminoglycans will also be studied in explant cultures of Bleomycin-treated and control lung tissues, with emphasis on determining glycosaminoglycan synthesis in discrete, localized areas of morphological abnormality. Glycosaminoglycan synthesis will also be demonstrated radioautographically, both in-vivo and in explant culture, to identify lung cells most actively secreting this connective tissue component in the normal and disease states. This method will also be used to determine possible interrelationships among glycosaminoglycans, collagen, and elastin as these components undergo rearrangement during the disease process. In addition, fibroblast cultures obtained from Bleomycin-treated and control lungs at various times following induction of the disease will be studied for glycosaminoglycan synthesis. Finally, the mode of action of Bleomycin in the lung will be investigated by measuring 3H-thymidine uptake radioautographically in both experimental and control animals. This multifaceted approach will hopefully shed light on the pathogenesis of interstitial lung disease.